This is a request for an ADAMHA Research Scientist Award (RSA). The long range goals are: l) identification of psychosocial factors that adversely affect the development and course of coronary heart disease and other life-threatening diseases; 2) elucidation of the biological mechanisms responsible for these adverse effects on health; and 3) the application of the knowledge gained to develop more effective means of prevention, treatment and rehabilitation. To achieve these goals, over the next 5 years a broad-ranging program of research will: 1) use epidemiologic methods to determine the role of health-damaging psychosocial factors like hostility, social isolation, depression, and job strain in the development and course of CHD and other major illness; 2) use techniques from neurobiology, biological psychiatry, and molecular biology to identify the biological mechanisms -- with special emphasis on the role of brain serotonergic function and the molecular biology of macrophage activation - - whereby these psychosocial factors harm health; and 3) develop and evaluate both behavioral and pharmacologic means to ameliorate the health- damaging effects of the psychosocial factors.